β3‐Adrenergic Activation Improves Maternal and Offspring Perinatal Outcomes in Diet‐Induced Prepregnancy Obesity in Mice

Objective: Prepregnancy obesity is an epidemic disorder that seriously threatens both maternal and offspring health. This study investigated the effects of β3-adrenergic receptor (β3-AR) activation on the perinatal outcomes in a diet-induced prepregnancy obese (PPO) murine model. Methods: Four-week-old female C57BL/6 mice were fed high-fat diet or chow diet for 16 weeks to yield PPO mice and chow-fed (CF) lean mice, respectively. After successful mating with CF males, the PPO and CF mice were both randomly divided into vehicle control- or CL316,243 (a highly selective β3-AR agonist)- treated groups. On gestational day 7, subcutaneous infusion of CL316,243 or saline vehicle (1 mg/kg/d) was provided using osmotic pumps. The perinatal outcomes, adipose tissue morphology, and metabolic and inflammatory markers were examined. Results: Chronic β3-AR agonist infusion induced brown adipose tissue activation and white adipose tissue browning and countered obesity-induced alterations in lipid profiles, insulin resistance, and systemic and local inflammatory states. Moreover, β3-AR activation was associated with improved placental perfusion and offspring outcomes. Conclusions: Our results provide proof-of-principle evidence that pharmacological β3-AR activation may be of therapeutic potential in preventing prepregnancy-obesity-associated adverse maternal and offspring perinatal outcomes. Obesity